Effects and Safety of Different Dose of Bambuterol on Chinese COPD Patients

A 12-week, Double-blind, Multicenter, 3-crossover, Placebo Controlled and Randomized Trial to Investigate the Efficacy and Safety of 10mg and 5mg Bambuterol Tablets Once Daily in Patients With Chronic Obstructive Pulmonary Disease (COPD)

This is a randomized, double-blind, 3-crossover trial with a 7-days washout baseline period followed by three treatment periods of 21-days each performed in patients with COPD. Patients will be randomized to receive three treatments (bambuterol 10mg, bambuterol 5 mg and placebo).

Patients with COPD who meet the inclusion criteria will enter the 7-days washout baseline period. After the baseline period, patients will be randomly assigned to one of the following treatment sequences:

• Sequence I: bambuterol 10mg (21 days) -washout (7 days) - bambuterol 5mg (21 days) - washout (7 days) - placebo (21 days);
• Sequence II: bambuterol 5mg (21 days) -washout (7 days) - placebo (21 days) - washout (7 days) - bambuterol 10mg (21 days) ;
• Sequence III: placebo (21 days) -washout (7 days) - bambuterol 10mg (21 days) - washout (7 days) - bambuterol 5mg (21 days).

During the treatment period patients will record their adverse events and use of rescue medication (Ipratropium bromide) in a diary. At each visit, pulmonary function tests will be performed. At V2, V4 and V6, forced expiratory volume at one second (FEV1) and forced vital capacity (FVC) are measured at following times: immediately before tablet treatment, and at 0.5, 1, 2, 3, 4, 6, 9, 12hrs after administration of tablets, FEV1 and FVC area under curve (AUC) 0~12 hours will be analyzed. At V1, V3, V5 and V7, and FVC are measured a time in the morning. Peak expiratory flow rate (PEFR) is measured by Mini-Wright peak flow meter in the morning before treatments. All other data will be evaluated as safety status, and monitoring of adverse events.

Inclusion Criteria:

• COPD, the disease is under a stable phase
• Giving written informed consent
• Age 40 - 80 years (both inclusive)
• Chinese ethnicity
• 30% of predicated normal ≤Post bronchodilator FEV1 ≤ 70% of predicated normal
• Post bronchodilator FEV1/FVC ≤ 70% (Note: post bronchodilator FEV1 will be tested 20-30 minutes after Salbutamol is used (inhaled via metered dose inhaler (MDI) and spacer).

Exclusion Criteria:

• COPD acute exacerbation 4 weeks prior to the enrollment
• Patients with a history of asthma, allergic rhinitis, atopy
• Use of disallowed drugs
• Clinically relevant abnormal laboratory values suggesting an undiagnosed disease requiring further clinical evaluation (as assessed by the Investigator)
• Severe psychiatric or neurological disorders
• Congestive heart failure severity grade IV according to New York Heart Association (NYHA)
• Haemodynamically significant cardiac arrhythmias or heart valve deformations
• CT or X-ray findings indicating an acute pulmonary disease other than COPD (e.g. tuberculosis, severe bronchiectasis, tumors)
• Severe immunological diseases (e.g. HIV infection, multiple sclerosis, lupus erythematosus, progressive multifocal leukoencephalopathy)
• Severe acute infectious diseases (e.g. tuberculosis or acute hepatitis)
• Any diagnosis of a malignant disease (except basal cell carcinoma) within 5 years before trial start
• Alcohol or drug abuse within the past year
• Suspected hypersensitivity to the Bambuterol or ingredients thereof, or any other contraindication for the use thereof
• Pregnancy, breast feeding, planned oocyte donation or oocyte implantation
• Participation in another trial (use of investigational product) within 30 days preceding the baseline visit V1 or re-entry of patients previously enrolled in this trial
• Suffering from any concomitant disease that might interfere with trial procedures or evaluations